Dosage forms, often manufactured in the shape of a compressed single layered tablet, comprising a cellulose ether are known to the pharmaceutical drug dispensing art. For example, dosage forms comprising the cellulose ether hydroxypropylmethylcellulose are disclosed in U.S. Pat. Nos. 3,870,790; 4,140,755; 4,167,588; 4,226,849; 4,259,314; 4,357,469; 4,369,172; 4,389,393 and U.S. Pat. No. 4,540,566.
While the dosage forms known to the prior art use the cellulose ether hydroxypropylmethylcellulose there are major disadvantages associated with the prior art dosage forms. For instance, the mechanical integrity of some prior art dosage forms often is insufficient to provide both a sustained and a controlled release of drug over a prolonged period of time. The prior art dosage forms often exhibit insufficient mechanical integrity, that is, the ability to stay together in a moving fluid environment such as the gastrointestinal tract, without prematurely breaking-up and thereby prematurely releasing all of its drug. The above-mentioned desirable properties of sustained and controlled release are not apparent in the prior art dosage forms that undergo substantial disintegration, often in less than eight hours, in a fluid environment of use.
Another disadvantage associated with the prior art dosage forms is that the dosage forms frequently exhibit an unwanted, variable and difficult to reproduce drug release rate pattern. For example, the prior art dosage forms comprising a small amount of a cellulose ether frequently exhibit the above behavior, such as those dosage forms containing less than five weight percent (wt %) hydroxypropylmethylcellulose having a molecular weight greater than 50,000 grams per mole and blended with a hydroxypropylmethylcellulose having a molecular weight much less than 50,000. The presence of the high molecular weight polymer in the dosage form masks the release characteristics of the low molecular weight polymer in the dosage form resulting in an erratic release rate pattern which is difficult to reproduce from dosage form to dosage form and from batch to batch comprising the dosage forms.
Still other disadvantages associated with the prior art dosage forms are that the dosage form over its shelf-life can exhibit an unpredictable change in its release rate characteristics; the prior art dosage forms, when tested in an in vitro test that substantially reproduces the in vivo environment of the gastrointestinal tract, often release the drug at a greater rate of release in vivo rather than in vitro, which difference can be attributed to a premature disintegration of the prior art dosage form; and, the prior art dosage form in a high shear fluid environment, such as the stomach, releases its drug too quickly, usually in less than four hours and it is, therefore, not adapted to prolonged drug release.
Thus, in the light of the above presentation, it will be appreciated by those versed in the dispensing art that if a novel dosage form is made available to the medical and pharmaceutical arts for dispensing difficult to deliver drugs essentially-free of the tribulation known to the prior art, such a dosage form would have a definite use and also would be a valuable contribution to the dispensing art. It will be further appreciated by those versed in the dispensing art that if a dosage form can be provided that (a) possesses desirable release rate and mechanical properties for dispensing a drug over a prolonged period of time, (b) provide instant drug availability and prolonged drug delivery from the same dosage form, and which dosage form (c) can be manufactured at an economical cost, such a dosage form would have a positive and a practical value and represent an advancement in the pharmaceutical arts.